A combined DPA1~DPB1 amino acid epitope is the primary unit of selection on the HLA-DP heterodimer. Immunogenetics 2012 Aug;64(8):559-69
Date
04/25/2012Pubmed ID
22526601Pubmed Central ID
PMC3395342DOI
10.1007/s00251-012-0615-3Scopus ID
2-s2.0-84864282322 (requires institutional sign-in at Scopus site) 43 CitationsAbstract
Here, we present results for DPA1 and DPB1 four-digit allele-level typing in a large (n = 5,944) sample of unrelated European American stem cell donors previously characterized for other class I and class II loci. Examination of genetic data for both chains of the DP heterodimer in the largest cohort to date, at the amino acid epitope, allele, genotype, and haplotype level, allows new insights into the functional units of selection and association for the DP heterodimer. The data in this study suggest that for the DPA1-DPB1 heterodimer, the unit of selection is the combined amino acid epitope contributed by both the DPA1 and DPB1 genes, rather than the allele, and that patterns of LD are driven primarily by dimer stability and conformation of the P1 pocket. This may help explain the differential pattern of allele frequency distribution observed for this locus relative to the other class II loci. These findings further support the notion that allele-level associations in disease and transplantation may not be the most important unit of analysis, and that they should be considered instead in the molecular context.
Author List
Hollenbach JA, Madbouly A, Gragert L, Vierra-Green C, Flesch S, Spellman S, Begovich A, Noreen H, Trachtenberg E, Williams T, Yu N, Shaw B, Fleischhauer K, Fernandez-Vina M, Maiers MAuthor
Bronwen E. Shaw MBChB, PhD Center Director, Professor in the Medicine department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Amino AcidsEpitope Mapping
Epitopes
Gene Frequency
Genotype
HLA-DP alpha-Chains
HLA-DP beta-Chains
Haplotypes
Hematopoietic Stem Cells
Humans
Linkage Disequilibrium
Models, Molecular
Polymorphism, Genetic